This proposal aims to identify the neural substrate underlying the cognitive deficits of psychopathic offenders. Psychopathy is a personality disorder characterized by poor judgment, impulsive and violent antisocial behavior, substance abuse, and unstable, predatory relationships which are all very costly to society. The left hemisphere activation hypothesis (LHAH) and response modulation hypothesis (RMH) are two theoretical perspectives that explain many core features of psychopathy. According to these hypotheses, psychopaths'cognitive functions are not always impaired;their poor judgment and reckless behavior reflect situation-specific cognitive deficits. According to the LHAH, psychopaths'cognitive deficits reflect a dramatic deterioration in general cognitive efficiency in conditions that place substantial and differential demands on LH systems, including the pursuit of immediate tangible goals. According to the RMH, psychopaths exhibit a more specific difficulty in processing and using peripheral information in such situations. These hypotheses for state-dependent deficits are consistent with findings from many studies of psychopathy and make novel predictions for treatment. Although both hypotheses have implications for the neurobiological underpinnings of psychopathy, the anomalous brain activity underlying LHA and RM performance deficits is largely unknown. At the same time, prior neuroimaging studies have identified reduced activation in paralimbic areas in psychopathic offenders, which has led to development of the paralimbic hypothesis (PLH). The PLH suggests that psychopaths exhibit dysfunction of the paralimbic system. However, this hypothesis does not limit paralimbic system anomalies to specific conditions or specify how fMRI findings are related to behavioral deficits. In summary, substantial behavioral evidence corroborates the LHA and RM hypotheses and there is substantial fMRI evidence consistent with the PL hypothesis. However, few studies have examined whether any of these hypotheses could help to explain the empirical findings associated with one of the others. To establish the neurological bases underlying psychopathy and to test these three hypotheses simultaneously, this project examines regional brain activation while offenders and healthy controls complete cognitive and emotional tasks under conditions validated for activating hemisphere-specific systems. We will identify the neural substrates of LHA and RM deficits by identifying brain activation differences associated with psychopathy in approach motivation situations as predicted by the LHAH and RMH. We will examine whether these differences are specific to LHA and RM conditions and whether the pattern of anomalous activations is localized largely to PL versus other brain areas predicted by the LHAH and RMH. In examining whether predicted performance differences correlate with differences in brain activation and whether hemodynamic activity mediates relations between psychopathy and performance deficits, proposed studies will provide a foundation for a more integrated understanding of the pathophysiology of psychopathy. PUBLIC HEALTH RELEVANCE: Psychopathic individuals (as many as 2-3% of males) deceive, manipulate, and abuse their family members and romantic partners and account for a vastly disproportionate share of violent and nonviolent crime, making psychopathy a major public health problem. The left hemisphere activation and response modulation hypotheses are innovative dynamic hypotheses that provide persuasive explanations for psychopathic offenders'poor judgment and reckless behavior in situations presenting immediate tangible goals, but no prior studies have examined the relevance of these perspectives for brain activation in psychopathy;in contrast, prior imaging studies have yielded findings consistent with the paralimbic hypothesis but have not examined whether these findings depend on demands on left hemisphere systems or demands to modify ongoing responses. By testing all three theories simultaneously, this project will allow us to identify the brain areas that underlie cognitive deficits in psychopathic offenders and provide us with a more comprehensive understanding of the neural mechanisms underlying psychopathy so that these can be better targeted by interventions.